2. Biology of fusion in spine Autograft allograft and recent advances Technical aspects of bone graft harvest and complications

3. Spinal fusion 1911 Albee (Pott disease) Hibbs (scoliosis) Now treating more “discogenic back pain” www.srs.org www.allaboutsarasota.com/timeline2.htm

4. GRAFT INCORPORATION Depends on material, implant site, disease state. Following Implantation 1. Hematoma 2. Inflammation/MSC 3. Blood vessel invasion 4. Bone formation at graft surface

5. Inflammation stage - release of growth factors Collagen formation simultaneous with collagen degradation Mechanical Environment Tissue Quality…e.g. scar tissue, heart disease, immunocompromised, smokers, steroids

6. Decrease in trabecular bone volume and fusion mass Decrease osteoblast differentiation Calcitonin resistance Impaired vascularization Increase platelet aggregation and vasoconstriction

7. Three biological mechanism are involved: o Osteogenesis:  production of new bone by proliferation, osteoid production and mineralization o Osteoconduction:  production of new bone and migration of local osteocompetent cells along a conduit e.g. fibrin, blood vessel or even certain alloplast material like hydroxyapatite  Originate from the endosteum or residual periosteum of the host bone o Osteoinduction:  formation of bone by stem cells transforming into osteocompetent cells by BMP  It induct the recipient tissue cells to form periosteum and endosteum

8. The basis of spinal fusion is bone formation in an osteoconductive environment by osteoprogenitor cells induced by osteoinductive agents The success of spinal fusion also depends on anatomical location biomechanical environment surgical approach internal fixation

9. COMBINATION of: o Vascularity o Stability o Progenitor cells o Structural matrix o Growth factors NET BIOLOGIC ACTIVITY SUM of: o Inherent biologic activity o Living cells and products o Osteoinduction capacity o Osteoconduction capacity o Capacity of the surrounding tissues to activate the process

10. DEFICIENCIES of: o Vascularity o Stability o Progenitor cells o Structural matrix o Growth factors

11. WHAT IS A BONE GRAFT Word ‘graft’ conjures image of transplant tissue, not true but is the terminology used. Any implanted material that alone or in combination promotes a healing response by osteogenic, osteoconductive or osteoinductive activity….

12. Vast number of : o Dental o Basic Science/Animal o Spine o Small series o Review articles 46% 25% 11% 5% 14%

13. Without a good host and host bed ANY material WILL FAIL!

14. Obesity Smoking

15. The graft must supply that which the host lacks…… The host must supply that which is not inherent to the graft!!

16. Biocompatible Bioresorbable Osteoconductive Osteoinductive Easy to use Cost effective

17. Autograft Growth Factors Allograft Biosynthetic Composite Future?

18. GOLD STANDARD Osteoconductive o Hydroxyapatite, Collagen Osteoinductive o BMP, TGF-B Osteogenic o Osteoprogenitor cells

19. Ideal Bone Graft Substitute Biocompatible Bioresorbable Osteoconductive Osteoinductive Easy to use Cost effective ADVANTAGES Histocompatible No risk of transmissible disease Osteogenic cells and proteins Rapid incorporation Structural, workable

20. LIMITATIONS o Limited Quantity o Limited Structure and shape o Variable osteogenic potential o DONOR SITE MORBIDITY- 2-35%!

21. Autogenous bone marrow aspirated from iliac crest or vertebral bodies - potentially osteogenic cells Pluripotential stem cells- differentiation along osteoblast lineage Initial 2 ml = 2400 alkaline phosphatase-positive colony forming units >2 ml -rapid reduction concentration of stem cells Easy harvest Low potency, potency decreases with age Commercial growth factors- doubtful efficacy

22. TYPES (Properties determined by processing) Fresh o problems availability, compatibility, storage &disease Frozen o <-60*c Freeze dried o water removed &vacuum sealed Demineralized Bone Matrix (DBM)

23. ADVANTAGES o Unlimited quantity o Multiple sizes, shapes, forms o Structural o Workable o Osteoconductive o Osteoinductive? INDICATIONS o Large structural defects o Filler / support o Autogenous graft expander? o Cortical/cartilage defects

24. Limitations  Disease transmission (HIV 1:1,000,000)  Histocompatibility  Improved with freezing & processing  Problems with incorporation  Weakens with revascularization  Reliant on a favorable host bed Rejection  Class I & II histocompatibility complex antigens  Animal studies suggest there is significant response. In humans HLA antibodies are detected but results good.  Sensitization against other grafts

25. VertiGraft is a line of allograft bone wedges and shafts designed to provide anterior column support in spinal procedures. Types of bone used include femur, fibula, and humerus. Reprinted, with permission, from DePuy-AcroMed Inc., Raynham, MA.

26. Noncollagenous protein, BMPs, Type-1 collagen Acid extraction of allograft bone Osteoconduction Limited osteoinductive capacity Various forms Easily stored, readily available

27. INDICATIONS o Small stable defects o Autogenous graft expander o Allograft enhancer LIMITATIONS o Not structural o Not workable o Not osteogenic o Minimal osteoconductive o Variable osteoinductive capacity

28. One Level 1 study in spine showing equivalent rates of fusion using autograft versus autograft and DBM Evidence shows differential potencies from lot to lot and manufacturer! Considered reprocessed material

29. CERAMICS o Osteoconductive Matrix o Composition  Hydroxyapatite (HA)  Calcium Phosphate  Calcium Sulfate  Tricalcium phosphate (TCP)  Combinations o Varying pore size and interconnectivity

30. Pro Osteon is harvested from marine coral exoskeletons that are exothermally converted to hydroxyapatite. The interconnected porous structure closely resembles the porosity of human cancellous or cortical bone. Reprinted, with permission, from Interspore Cross International, Irvine, CA.

31. Indications o Small stable defects o Graft expander or filler o Use with BMP o Antibiotic delivery o Availability o Osteoconductive Multiple sizes and shapes Structural Potentiate BMPs Advantages

32. Collagen + Ceramic+ Hydroxyapatite Multiple compositions Osteoconductive Osteoinductive Paste or strips Malleable Collagraft strip is comprised of collagen and a composite mineral of hydroxyapatite and tricalcium phosphate. Reprinted, with permission, from NeuColl Inc.,Campbell, CA.

33. These are included in the TGF-β family o Except BMP-1 BMP2-7,9 are osteoinductive BMP2,6, & 9 may be the most potent in osteoblastic differentiation Follow a dose/response ratio

34. BMP-2 o Increased fusion rate in spinal fusion o Role for improved wound healing? o Role for reducing infection? BMP-7 equally effective as iliac crest bone graft in nonunion Must be applied locally because of rapid systemic clearance Protein therapy vs gene therapy

36. Depends on location and type of fusion  Cortical bone for mechanical strength and structural support  Cancellous bone for osteogenic potential  Cortico-cancellous bone for metal/carbon cages filled with bone chips

37. Cancellous bone  All 3 char.  Nidus for bone formation  Poor wt. bearing  Fails under compression  Used as – Onlay graft over post elements Packed into facet joints Along with cortical bone or load bearing device in interspace  less osteoinductive and osteogenic  Good wt. bearing  Resist compression- interbody graft  Combination with cancellous augments osteoinductive and osteogenic potential Cortical bone

38. The iliac crest Most common source in neurosurgery

39. Hip Bone: o Made of three bones fused in a Y-shaped fashion

40. Bone harvesting: o The lateral approach to the anterior ilium affect the gait the most o The medial anterior approach involve the large iliacus muscle which is not necessary for normal gait but large medial hematoma might produce gait disturbances

41. Surgical access: o Incision should be placed 1 inch posterior to ASIS and extend to iliac tubercle o placed lateral to bony prominence to prevent irritation by tight clothes or belt o Proceed down to bone medial to the muscles, tensor fascia lata and gluteus medius and lateral to the iliacus and the external abdominal muscles

42. Cancellous bone is available in the anterior ilium within the upper 2 – 3 cm and between the tubercle and the anterior superior spine, Iliac crest graft. During closure, strict attention to reorient and reposition the muscles in their original positions Hemostasis of raw bony surface – gelfoam preferred over bone wax – allows reuse of donor site in future A drain is required because of the dead space and should be placed within the bony cavity

43. Acquired bowel herniation ( larger donor sites (>4 cm))-20 cases reported in the literature Meralgia paresthetica (injury to the lateral femoral cutaneous nerve also called Bernhardt-Roth's syndrome) Meralgia parestheticalateral femoral cutaneous nerve Pelvic instability Fracture (extremely rare) Fracture Injury to the clunial nerves (this will cause posterior pelvic pain which is worsened by sitting)clunial nerves Injury to the ilioinguinal nerveilioinguinal nerve Infection Minor hematoma (a common occurrence)hematoma Deep hematoma requiring surgical interventionhematoma Seroma

44. Ureteral injury Ureteral Pseudo aneurysm of iliac artery (rare) Tumor transplantation Cosmetic defects (chiefly caused by not preserving the superior pelvic brim) Chronic pain Bone grafts harvested from the posterior iliac crest in general have less morbidity, but depending on the type of surgery, may require a flap while the patient is under GA

45. Right rib is always preferred because: Postoperative pain is less likely to be confused with cardiogenic pain Rib harvesting: o Usually 5th or 6th typical one o Incision is placed in the infra-mammary crease, to hide the scar o Usually during thoracotomy

46. Success rates with other sources of allograft and autograft struts has made it unnecessary to harvest rib grafts through a separate incision Convenient during limited thoracic reconstruction because graft can be harvested during thoracotomy

47. The tibia The extensive subcutaneous surface of the tibia makes it an accessible donor site for bone grafts

48. Bone harvesting: o The tibial plateau is an excellent reservoir for cancellous bone o It can provide up to 40 cc of bone without affecting the structural support of the tibia

49.  Surgical access:  Could be done under local anesthesia and conscious sedation  Incision over the lateral tubercle best accomplished by flexing the leg at the knee joint  It is 6 – 10 mm from the skin and dissection is made through the thin subcutaneous tissue  Sharp dissection to reflect the tensor fascia lata band and make 1 cm opening into the cortex and the cancellous bone could be harvested lateral and inferior to the midline to avoid damage to the knee

50. Used in past as strut graft Microvascular anastomosis – vascularized fibular strut graft Not gained widespread acceptance- Success rate of cervical fusion is quite high using nonvascularized fibular auto/allograft with appropriate stabilization

51. Thank You